Imaging CXCL12-CXCR4 Signaling in Ovarian Cancer Therapy

Salomonnson, Emma; Stacer, Amanda C.; Ehrlich, Anna; Luker, Kathryn E.

doi:10.1371/journal.pone.0051500

Cited by 31 publications

(21 citation statements)

References 39 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For a long time, CXCR4 was considered as a unique receptor of CXCL12. CXCL12-CXCR4 axis plays an important role in the invasion and metastasis of multiple malignancies, including lung cancer, ovarian cancer, glioblastoma, and liver cancer, and is closely associated with the prognosis of cancer patients [3][4][5]. The long-held exclusivity of the CXCL12-CXCR4 interaction has been ended with the identification of CXCR7 as an alternative CXCL12 receptor which shows high binding affinity for CXCL12 [6].…”

Section: Introductionmentioning

confidence: 99%

CXCL12-CXCR4/CXCR7 axis contributes to cell motilities of oral squamous cell carcinoma

et al. 2015

View full text Add to dashboard Cite

The chemokine CXCL12 and its receptors CXCR4 and CXCR7 might play important roles in the occurrence and development of oral squamous cell carcinoma (OSCC). While CXCR4 expression is associated to initiation and progression of OSCC, the role of CXCR7, the recently founded second CXCL12 receptor, has not yet been elucidated in OSCC. In this study, CXCR4 and CXCR7 expressions were evaluated using western blot and quantitative RT-PCR in OSCC cells. AMD3100 (CXCR4 antagonist) was used to inhibit the activation of CXCR4. In contrast to CXCR4, effective CXCR7 small interfering RNA (siRNA) segments were used to silence CXCR7 in OSCC cells. The biological effects of CXCL12-CXCR4/CXCR7 axis on OSCC cell lines were studied by CCK-8 and transwell assay. As determined by RT-PCR and Western blot, CXCR7 expression was significantly downregulated after siRNA transfection in OSCC cells, and thus significantly promoted OSCC cell migration and invasion in vitro. The relative roles of the two CXCL12 receptors were further assessed by CXCR7 knockdown or deactivate CXCR4 receptor alone, or in combination, in the OSCC cells. In vitro functional analyses indicated that, in response to their common ligand (CXCL12), both receptors induced inhibition of proliferation and migration in OSCC cells in a dose-dependent manner. Exogenous CXCL12 could promote cell migration and invasion. In conclusion, our results indicated that CXCL12 which combined its receptor CXCR4 and CXCR7 together could promote cell motilities of OSCC.

show abstract

Section: Introductionmentioning

confidence: 99%

CXCL12-CXCR4/CXCR7 axis contributes to cell motilities of oral squamous cell carcinoma

et al. 2015

View full text Add to dashboard Cite

show abstract

“…To quantify association of CXCR4 with β-arrestin 2, we used a click beetle luciferase complementation assay developed by our group in which CXCR4 and β-arrestin 2 are fused to amino (N)- and carboxy (C)-terminal luciferase fragments, respectively [34]. Interaction of CXCR4 with β-arrestin 2 reconstitutes luciferase activity, producing a bioluminescent readout of CXCL12-CXCR4 signaling to β-arrestin 2.…”

Section: Resultsmentioning

confidence: 99%

Allosteric peptide regulators of chemokine receptors CXCR4 and CXCR7

Ehrlich

Ray

Luker

et al. 2013

Biochemical Pharmacology

Self Cite

View full text Add to dashboard Cite

The chemokine CXCL12 and its shared seven-transmembrane receptors CXCR4 and CXCR7 regulate diseases including cancer, atherosclerosis, autoimmunity, and HIV infection, making these molecules promising drug targets. These molecules also control key processes in normal development and physiology, suggesting the need to selectively modulate CXCR4 and/or CXCR7 functions and signaling to reduce potential complications of long-term therapy. We previously identified two peptides that functioned as allosteric agonists driving CXCR4-dependent chemotaxis, providing key structural information to design a small number of additional peptides to investigate determinants of CXCL12 interactions and signaling through CXCR4 and CXCR7. In the current study, we show that the previously identified peptides only minimally activated CXCR4 signaling through the cytosolic adapter protein β-arrestin 2 and do not initiate signaling to ERK1/2. By comparison, peptides with diverse N-terminal amino acid sequences effectively activated CXCR7 signaling to β-arrestin 2. One peptide, designated as GSLW based on its N-terminal amino acids, activated CXCR7 signaling and potentiated CXCL12-CXCR7 signaling without blocking the scavenger function of CXCR7 to internalize CXCL12. These results advance our understanding of CXCR7 ligand recognition and signaling, and provide structural information to target allosteric binding sites on this receptor as chemical probes and potential therapeutic agents.

show abstract

“…It is well acknowledged that SDF-1 mediates a large number of crucial biological processes such as neuronal and cardiac development, angiogenesis, apoptosis, and stem cell motility [16]. Substantial evidence indicates that SDF-1 can mediate the activation of SDF-1/CRCR4-PI3-MARK-NF-κB pathway, PI3K/Akt, Wnt, and ERK pathways, and further promotes the invasion and progression of cancers [17–19]. SDF-1 can also improve the expression of MMPs and VEGF, which are crucial for the aggressive behavior of cancers [9,20].…”

Section: Discussionmentioning

confidence: 99%

High Expression of Stromal Cell-Derived Factor 1 (SDF-1) and NF-κB Predicts Poor Prognosis in Cervical Cancer

Song

Zhang

et al. 2017

Med Sci Monit

View full text Add to dashboard Cite

BackgroundSDF-1 and NF-κB are associated with the prognosis of a wide range of cancers, but their value in cervical cancer remains controversial. The aim of this study was to investigate the expression of SDF-1and NF-κB in cervical cancer and their significance in clinical prognosis.Material/MethodsThe expression of SDF-1and NF-κB in 105 formalin-fixed, paraffin-embedded cervical cancer tissues and the adjacent tissues was examined by immunohistochemistry (IHC). The results were semi-quantitatively scored and analyzed by chi-square test. The overall survival times (OS) were collected by follow-up and analyzed by Kaplan-Meier analysis.ResultsThe expression level of both SDF-1and NF-κB in cervical cancer are higher than that in the adjacent tissues (P<0.05). SDF-1 expression are correlated with tumor size and FIGO histology grade (P<0.05). NF-κB expression are correlated with tumor size and FIGO histology grade, and lymph node metastasis (LNM) status (P<0.05). The patients with a positive expression of SDF-1or NF-κB tended to have much shorter survival time than patients with negative expression. In addition, multivariate Cox regression analysis demonstrated that SDF-1 expression and lymph node metastasis are independent predictors of the OS in cervical cancer patients.ConclusionsThe expression of SDF-1 is significantly associated with tumor size and FIGO histology grade. The expression of NF-κB is significantly associated with tumor size, FIGO histology grade, and lymph node metastasis. The positive SDF-1or NF-κB expression is significantly correlated with poor prognosis. These may be valuable biomarkers for the prognosis and the potential therapeutic targets of cervical cancer.

show abstract

Imaging CXCL12-CXCR4 Signaling in Ovarian Cancer Therapy

Cited by 31 publications

References 39 publications

CXCL12-CXCR4/CXCR7 axis contributes to cell motilities of oral squamous cell carcinoma

CXCL12-CXCR4/CXCR7 axis contributes to cell motilities of oral squamous cell carcinoma

Allosteric peptide regulators of chemokine receptors CXCR4 and CXCR7

High Expression of Stromal Cell-Derived Factor 1 (SDF-1) and NF-κB Predicts Poor Prognosis in Cervical Cancer

Contact Info

Product

Resources

About